Venous valve with sinus

ABSTRACT

A venous valve-with a structural member and valve leaflets that provide a sinus.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in Part of U.S. application Ser. No. 11/232,403, filed Sep. 21, 2005, the specification of which is incorporated by reference herein.

FIELD OF THE DISCLOSURE

The present disclosure relates to vascular medical devices and methods; and more particularly to venous valves and methods for forming the venous valve frame.

BACKGROUND OF THE DISCLOSURE

Venous blood flow returns de-oxygenated blood from the distal extremities to the heart via two mechanisms. The first is the perfusion pressure resulting from the arterial blood flow through tissue to the venous circulation system. Where arterial pressure prior to perfusion may be 60 to 200 mm Hg, the resulting venous pressure is typically 10 to 40 mm Hg. The second mechanism is the calf muscle, which, when contracted, compresses the veins (tibial and peroneal) overlying the bone and, through a system of valves, directs blood flow toward the heart. This is the organized flow of blood through a normal, healthy person.

Venous valves, especially those in the upper leg, perform an important function. When a person rises from a seated to a standing position, arterial blood pressure increases instantaneously to insure adequate perfusion to the brain and other critical organs. In the legs and arms, the transit time of this increased arterial pressure is delayed, resulting in a temporary drop in venous pressure. Venous pressure drops as blood flow responds to body position change and gravity, thereby reducing the volume of blood available to the heart and possibly reducing the flow of oxygenated blood to the brain. In such a case, a person could become light headed, dizzy, or experience syncope. It is the function of valves in the iliac, femoral and, to a lesser degree, more distal vein valves to detect these drops in pressure and resulting change of direction of blood flow and to close to prevent blood from pooling in the legs to maintain blood volume in the heart and head. The valves reopen and the system returns to normal forward flow when the reflected arterial pressure again appears in the venous circulation. Compromised valves, however, would allow reverse blood flow and pooling in the lower legs resulting in swelling and ulcers of the leg. The absence of functioning venous valves can lead to chronic venous insufficiency.

Techniques for both repairing and replacing the valves exist, but are tedious and require invasive surgical procedures. Direct and indirect valvuoplasty procedures are used to repair damaged valves. Transposition and transplantation are used to replace an incompetent valve. Transposition involves moving a vein with an incompetent valve to a site with a competent valve. Transplantation replaces an incompetent valve with a harvested valve from another venous site.

Prosthetic valves can be transplanted into the venous system, but current devices are not successful enough to see widespread usage. One reason for this is the very high percentage of prosthetic valves reported with leaflet functional failures due to excessive protein deposit, cell growth and thickening, and thrombosis. These failures have been blamed primarily on improper sizing and tilted deployment of the prosthetic valve. In addition, a great number of the valve leaflets come into close proximity to or in contact with the adjacent vessel wall, conduit, or supporting frame of the valve. Such contact or proximity can cause regions of blood stasis or near stasis, and can result in increased thrombus formation. In addition, contact can result in disruption of endothelial or other tissue at the contact point, further increasing the likelihood of thrombosis or increased tissue deposits or healing response. Further, such contact or proximity can result in valve leaflet(s) being stuck to the vessel wall, or otherwise unable to move properly, thereby rendering the valve less functional or completely non-functional.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the venous valve of the present disclosure.

FIG. 2 illustrates an elevation view of a section of the venous valve illustrated in FIG. 1.

FIG. 3 illustrates a plan view of a section of the venous valve, specifically the bottom half of the venous valve illustrated in FIG. 1.

DETAILED DESCRIPTION

Embodiments of the present disclosure are directed to vascular medical devices and methods for valve replacement and/or augmentation. Particularly, the present disclosure provides venous valves and methods for forming the venous valve. Various embodiments of the present disclosure can be used to replace and/or augment an incompetent valve in a body lumen. As used herein, “body lumen” can include, but is not limited to, veins, arteries, lymph vessels, ureter, cerebrospinal fluid track, or other body cavity, vessel, or duct.

Embodiments of the venous valve include a venous valve frame and valve leaflets that can be implanted through minimally-invasive techniques into the body lumen. In one example, embodiments of the apparatus and method for valve replacement or augmentation may help to maintain antegrade blood flow, while decreasing retrograde blood flow in a venous system of individuals having venous insufficiency, such as venous insufficiency in the legs. Use of valve embodiments can also be possible in other portions of the vasculature.

The figures herein follow a numbering convention in which the first digit or digits correspond to the drawing figure number and the remaining digits identify an element or component in the drawing. Similar elements or components between different figures may be identified by the use of similar digits. For example, 110 may reference element “10” in FIG. 1, and a similar element may be referenced as 210 in FIG. 2. As will be appreciated, elements shown in the various embodiments herein can be added, exchanged, and/or eliminated so as to provide a number of additional embodiments of valve. In addition, discussion of features and/or attributes for an element with respect to one Figure can also apply to the element shown in one or more additional Figures. Embodiments illustrated in the figures are not necessarily to scale.

FIG. 1 provides an illustration of various embodiments of a venous valve 100 of the present disclosure. The venous valve 100 can be implanted within the fluid passageway of a body lumen, such as for replacement and/or augmentation of a valve structure within the body lumen (e.g., a venous valve). In one embodiment, the venous valve 100 of the present disclosure may be beneficial to regulate the flow of a bodily fluid through the body lumen in a single direction.

FIG. 1 provides a top view of the venous valve 100 with a frame 102 being generally shown as a tubular body. While frame 102 is shown as a tubular body for illustrative purposes, the present disclosure contemplates that the frame 102 can have a number of different structural configurations that will be more fully discussed herein.

The frame 102 can have an inlet region 104 that defines an inlet cross sectional area 106, a middle region 108 that defines a middle cross sectional area 110, and an outlet region 112 that defines an outlet cross sectional area 114. As will be more fully discussed herein, various embodiments provide that the inlet cross-sectional area 106 can have a different relative size than the middle cross sectional area 110. In addition, the inlet cross sectional area 106 can be at least approximately equal to the outlet cross sectional area 114. Other relative relationships, as discussed herein, are also possible.

The venous valve 100 also includes valve leaflets 116 at least partially connected to the frame 102. The valve leaflets 116 include a first inflow surface 118, a first outflow surface 120 opposite the first inflow surface 118 and a free edge 122. In one embodiment, the valve leaflets 116 are configured to shift between an open position, shown with a broken line 124 in FIG. 1, and a closed position, shown with a solid line 126. The free edge 122 of the valve leaflet 116 helps define a free edge cross sectional area 128.

The material of the valve leaflets 116 can be connected to the frame 102 in a variety of ways so as to provide the various embodiments of the venous valve 100 of the present disclosure. For example, a variety of fasteners can be used to couple the material of the valve leaflets 116 to the frame 102 so as to form the venous valve 100. Suitable fasteners can include, but are not limited to, biocompatible staples, glues, sutures, or combinations thereof. In an additional embodiment, the material of the valve leaflets 116 can be coupled to the frame 102 through the use of heat sealing, solvent bonding, adhesive bonding, or welding the material of the valve leaflets 116 to either a portion of the valve leaflets 116 (i.e., itself) and/or the frame 102.

As illustrated in FIG. 1, the valve leaflets 116 can be coupled to at least a portion of the valve frame 102. As illustrated, the valve leaflets 116 can move relative the valve frame 102. The valve leaflets 116 can be unbound (i.e., unsupported) by the frame 102 and can extend between opposite sides of the frame 102 in the middle region 108. This configuration permits the valve leaflets 116 to move (e.g., pivot) relative the opposite sides of the frame 102 in the middle region 108 to allow a commissure 129 to reversibly open and close for unidirectional flow of the liquid through the venous valve 100.

Valve 100 provides an embodiment in which the surfaces defining the commissure 129 provide a bi-leaflet configuration (i.e., a bicuspid valve) for valve 100. Although the embodiments in FIG. 1 illustrate and describe a bi-leaflet configuration for the valve of the present disclosure, designs employing a different number of valve leaflets (e.g., tri-leaflet valve) may be possible. For example, additional connection points (e.g., three or more) could be used to provide additional valve leaflets (e.g., a tri-leaflet valve).

In addition, embodiments of the present disclosure couple the valve leaflets 116 to the frame 102 in a way such that the valve leaflets 116 in the closed position 126 form a fluid tight commissure 129.

The relationship between the valve leaflets 116 and the frame 102 also help to define a sinus region 130. As illustrated, the sinus region 130 can be defined by a volume 132 between the frame 102 and the valve leaflets 116 extending from an attachment location 134 to the free edge 122 while in the open position.

In one embodiment, the sinus region 130 can perform a variety of functions for the venous valve 100. For example, the sinus region 130 can allow for blood moving through the venous valve 100 to backwash into and through the sinus region 130. While not wishing to be bound by theory, the formation of the backwash into and through the sinus region 130 is a result of a separation of the blood flow as it moves past the free edge 122 of the valve leaflets 116. Separation occurs due to the extreme change in cross sectional area as the blood emerges from the free edge cross-sectional area 128 into the area defined by the middle cross-section 110. This separation forms eddy currents 136 that wash back into the sinus region 130 keeping both constant blood flow through the sinus region 130 and separating the valve leaflets 116 from the frame 102 and the native vessel wall. This latter feature helps to minimize the likelihood that the valve leaflets 116 will adhere to the frame 102 and/or any of the native vessel wall in which the venous valve 100 is placed.

The sinus region 130 also allows for improved valve leaflet 116 dynamics (e.g., opening and closing of the valve leaflets). For example, the sinus region 130 can allow for pressure differentials across the surfaces of the valve leaflets 116 that provide for more rapid closing of the valve leaflets 116 as the retrograde blood flow begins, as will be discussed herein.

As discussed herein, the presence of the sinus region 130 allows slower moving blood (e.g., backwash) to move into the sinus region 130 and faster moving blood on the first inflow surface 118 to create a pressure differential. This pressure differential across the valve leaflets 116 provides for a Bernoulli effect. The Bernoulli principle provides that the sum of all forms of energy in a fluid flowing along an enclosed path (e.g., the venous valve 100 positioned within a vein) is the same at any two points in that path. As discussed herein, the velocity of blood flow across the first inflow surface 118 of the valve leaflets 116 is greater than the velocity of blood flow across the outflow surface 120 of the valve leaflets 116. The result is a larger fluid pressure on the outflow surface 120 as compared to the first inflow surface 118. So, when blood flow slows through the valve, the fluid pressure on the first outflow surface 120 becomes larger than the fluid pressure on the first inflow surface 118 and the valve leaflets 116 have a natural tendency to “shut.”

The valve leaflets 116 of the present disclosure are also configured to include a complex curvature which can be utilized to form a pocket when the venous valve 100 is in the closed position. The pocket is shaped synergistically to enhance the performance of the venous valve 100 with the sinus region 130, as discussed herein. As used herein, “pocket” means a portion of the valve leaflet 116 that is concave when in the closed position 126 and distends when in the open position 124.

In one embodiment, the free edge 122 of the valve leaflets 116 can be positioned at a predetermined location 138 along the middle region 108 of the frame 102. For example, the predetermined location 138 can be positioned approximately at the maximum dimension of the middle cross section 110. Other predetermined locations 138 include those in the middle region 108 that are closer to the inlet region 104 than the outlet region 112. Other predetermined locations 138 are also possible, as will be discussed herein. In addition, specific dimensional relationships for the valve leaflets 116 and the middle region 108 of the frame 102 exist. These relationships will be discussed more fully herein.

According to the present disclosure, there are a variety of relative sizes for the inlet region 104, the middle region 108, and the outlet region 112 in association with the valve leaflets 116 that can provide for the backwash function of the sinus region 130. For example, as illustrated in FIG. 1, the inlet cross-sectional area 106, the free edge cross-sectional area 128 of the valve leaflets 116 in their open position, and the outlet cross-sectional area 114 all have approximately the same cross sectional area, whereas the middle cross-sectional area 110 has a larger relative cross sectional area. For example, in one embodiment, the relative diameters of the inlet region 104, middle region 108, and outlet region 112 are approximately equal to 1.0, 1.8, and 1.1, respectively. So, as blood flows past the free edge 122 of the valve leaflets 116, the blood flow separates, forming eddy currents 136 that provide at least in part, the backwash in the sinus region 130.

In an alternative embodiment, other configurations of the comparative sizes of the inlet, middle, free edge, and outlet cross-sectional areas 106, 110, 128, and 114 are possible that can provide for the backwash function of the sinus region 130. For example, both the middle and outlet cross-sectional areas 110, 114 can be larger than both the inlet cross-sectional area 106 and the free edge cross-sectional area 128 in its open position. In an alternative embodiment, the middle cross-sectional area 110 and the free edge cross-sectional area 128 in its open position can be smaller than both the inlet and the outlet cross-sectional areas 106, 114. In yet another embodiment, the free edge cross-sectional area 128 in its open position is smaller than both the middle and outlet cross-sectional areas 110, 114 while both the middle and outlet cross-sectional areas 110, 114 are smaller than the inlet cross-sectional area 106.

In the embodiments where the free edge cross-sectional area 128 in its open position is smaller than the inlet cross-sectional area 106, the Bernoulli principle, as discussed herein, provides that the fluid velocity increases as a result of the decrease in cross-sectional area. In these embodiments, the resulting increase in fluid velocity can provide enhanced recirculation and less thrombosis throughout the venous valve 100 due to increased blood flow velocity that effectively “flushes” thrombus and/or other material through and out of the venous valve 100. Additionally, in embodiments where the middle cross-sectional area 110 is smaller than the body lumen and the free edge cross-sectional area 128 in its open position is smaller than the inlet cross-sectional area 106, an increase in fluid velocity may help to “draw in” the tissue of the native vessel wall, creating a more fluid tight position for the venous valve 100 of the present disclosure. On the other hand, in these embodiments a prosthetic material can be provided to the treatment site to create a narrowing where the middle cross-sectional area 128 is to be positioned.

The free edge 122 of the valve leaflets 116 in their open configuration can define a number of different shapes, including round and non-round shapes. For example, the free edge 122 can define an eye shape or an oval shape. As will be appreciated, other shapes for the valve leaflets 116 in their open configuration are also possible.

In addition, the valve leaflets 116 are illustrated as being essentially of the same size and relative shape. This allows for a symmetrical configuration for the valve leaflets 116. Alternatively, the valve leaflets 116 can have a non-symmetrical configuration, where one of the valve leaflets 116 has at least one of a different size and/or shape as compared to another of the valve leaflets 116.

As illustrated, the frame 102 is shown having a circular peripheral shape. Other peripheral shapes for the frame 102 are possible. For example, peripheral shapes for the frame 102 can include not only circular, but elliptical, obround, conical, semi-conical, semi-spherical, polygonal, or combinations thereof. In one embodiment, polygonal shapes can include those defined generally with the struts to form, for example, triangular, tetragon (e.g., square or rectangular), pentagon, hexagon, and heptagon, among other polygonal shapes. Different combinations of these shapes for different regions 104, 108 and 112 are also possible.

Although the frame 102 can have many peripheral shapes including polygonal shapes, the functional shape of the frame 102 may change over time. For example, once the venous valve 100 is inserted into a body vessel, the body vessel wall will begin to form tissue deposits as it heals in and around the venous valve 100. As this occurs, the polygonal shape of the frame 102 may functionally change into more of a circular shape. Embodiments of the present disclosure take this process into account however, and remain functional despite potential in growth into the venous valve 100.

There are many ways in which the frame 102 may be formed. Generally, the frame 102 includes structural members 140 that define openings through the frame 102. One embodiment of the structural members 140 are shown partially in FIG. 1 forming the outlet region 112. As discussed herein, the frame 102 is shown as a tubular body for illustrative purposes; in addition, the structural members 140 as shown in the outlet region 112 are for illustrative purposes and are not meant to limit the configuration of the frame formed by the structural members 140.

In one embodiment, the structural members 140 of frame 102 are formed by cutting the openings in a contiguous tube of material to form the inlet, the middle, and the outlet regions 104, 108, 112 of the frame 102. Examples of techniques for cutting include laser cutting and/or water jet cutting. Other cutting techniques are also possible.

Different shapes and sizes for the regions 104, 108, and 112 can then be formed by stretching and/or deforming the structural members 140 to the desired shape and size. In one embodiment, the frame 102 can be positioned over a mandrel that defines the desired shape of the frame 102. Once positioned, the structural members 140 of the frame 102 can then be bent to conform to the shape of the mandrel. Alternatively, the structural members 140 of the frame 102 can be wound around the mandrel to form the desired configuration. The structural member 140 can then be processed according to the material type used. For example, the structural member 140 can be heat set on the mandrel to set the shape according to techniques as are known.

In an alternative embodiment, different portions of the frame 102 can be formed separately and then joined to form the frame 102. When the different regions are formed separately, the two portions can be joined by a welding technique, such as laser welding. Other welding or bonding techniques are also possible.

In one embodiment, the structural members 140 of the frame 102 are designed to provide a distribution of forces along the length of the frame 102. For example, the structural members 140 in the middle region 108 can be designed to provide an expansion force greater than the inlet and outlet regions 104, 112. The distribution of forces can be accomplished in various ways, including changing the spacing between the structural members 140 in the different regions (e.g., the inlet region 104, etc.), changing the number of structural members 140 in the different regions, by heat setting the structural members 140, or by changing the shape of the frame 102 in the different regions, among others.

As will be appreciated, differing cross-sectional shapes for the structural members 140 are possible, including but not limited to round (e.g., circular, oval, and/or elliptical), rectangular geometries having perpendicular sides, one or more convex sides, or one or more concave sides; semi-circular; triangular; tubular; I-shaped; T-shaped; and trapezoidal. The similarity and/or differences in the cross-sectional geometries and/or cross-sectional dimensions can be based on one or more desired functions to be elicited from each portion of the structural member 140.

As discussed, natural venous valves partially function via contraction of the calf muscles which compress the veins overlying the bones and direct blood flow toward the heart. Embodiments of the present disclosure, therefore, can be designed to either resist collapsing under the contraction of the muscle, or embodiments can be designed to collapse in a predetermined way while maintaining functionality, as further discussed herein.

In one embodiment, the frame 102 is designed to resist collapsing by providing a sufficient number of structural members 140 in a predetermined configuration so as to resist the prevailing radial pressures. By maintaining a relatively static configuration, the relationship between the valve leaflets 116 and the different regions (e.g., the inlet region 104, the middle region 108, etc.) Is controlled. Controlling the relationship between the valve leaflets 116 and the different regions (e.g., the inlet region 104, the middle region 108, etc.) Allows the valve leaflets 116 to operate more effectively. For example, by controlling the relationship of the valve leaflets 116 and the different regions (e.g., the inlet region 104, etc.) The size of the valve leaflets 116 can be minimized, thus decreasing the chance that a valve leaflet 116 will come into contact with the frame 102 and/or the native vessel wall.

In an alternative embodiment, the frame 102 can be configured to radially collapse at least partially when the calf muscle contracts over the vein. In one embodiment, the structural members 140 of the frame 102 can be configured to collapse in a predetermined direction so that the valve leaflets 116 are able to shift from the open position to the closed position as illustrated in FIG. 1 when the frame 102 is collapsed. For example, the structural members 140 of the frame 102 can be configured so that when the calf muscle contracts, some of the structural members 140 collapse radially inward in the middle region 108 to compress the sinus region 130. At the same time, other structural members 140 in the middle region 108 radially extend outward so that the attachment locations 134 at the free edges 122 of the valve leaflets 116 are stretched apart. Other configurations are also possible including structural members 140 collapsing in other regions of the frame 102 (e.g., inlet region 104 and outlet region 112) either in combination with the middle region 108 or alone.

The embodiments of the structural member 140 described herein can also be constructed of one or more of a number of materials and in a variety of configurations. The structural member 140 embodiments can have a unitary structure with an open frame configuration. The structural member 140 can also be self-expanding. Examples of self-expanding frames include those formed from temperature-sensitive memory alloy which changes shape at a designated temperature or temperature range, such as Nitinol. Alternatively, the self-expanding structural members 140 can include those having a spring-bias. In addition, the structural member 140 can have a configuration that allows the structural member 140 embodiments be radially expandable through the use of a balloon catheter.

The structural member 140 can be formed from a number of materials. For example, the structural member 140 can be formed from a biocompatible metal, metal alloy, polymeric material, or combination thereof. As described herein, the structural member 140 can be self-expanding or balloon expandable. In addition, as discussed herein, the structural member 140 can be configured so as to have the ability to move radially between the collapsed state and the expanded state. Examples of suitable materials include, but are not limited to, medical grade stainless steel (e.g., 316L), titanium, tantalum, platinum alloys, niobium alloys, cobalt alloys, alginate, or combinations thereof. Additional structural member 140 embodiments may be formed from a shape-memory material, such as shape memory plastics, polymers, and thermoplastic materials. Shape memory alloys having superelastic properties generally made from ratios of nickel and titanium, commonly known as Nitinol, are also possible materials. Other materials are also possible.

The venous valve 100 can further include one or more radiopaque markers (e.g., rivets, tabs, sleeves, welds). For example, one or more portions of the structural member can be formed from a radiopaque material. Radiopaque markers can be attached to, electroplated, dipped and/or coated onto one or more locations along the frame. Examples of radiopaque material include, but are not limited to, gold, tantalum, and platinum.

The position of the one or more radiopaque markers can be selected so as to provide information on the position, location, and orientation (e.g., axial, directional, and/or clocking position) of the valve 100 during its implantation. For example, radiopaque markers can be configured radially and longitudinally (e.g., around and along portions of the structural member 140) on predetermined portions of the structural member 140 to allow the radial and axial position of the structural member 140 to be determined. So in one embodiment a radiograph image of the structural member 140 taken perpendicular to the valve leaflets 116 in a first clock position can produce a first predetermined radiograph image (e.g., an imaging having the appearance of an inverted “Y”) and a radiographic image taken perpendicular to the commissure 129 in a second clock position can produce a second predetermined radiograph image (e.g., an imaging having the appearance of an upright “Y”) distinguishable from the first predetermined radiograph image.

FIG. 2 is an illustration of a portion of the venous valve cut along the longitudinal center axis 2-2 in FIG. 1 to show one valve leaflet 216 connected to the frame 202 in the open position, as discussed herein. As illustrated, the frame 202 provides for a longitudinal center axis 242 extending from the inlet region 204 to the outlet region 212. The longitudinal center axis 242 provides a reference point to assist in the definition of various features of the valve leaflets 216 in relation to the frame 202 in different regions of the valve (e.g., inlet region 204, middle region 208, etc.).

As discussed herein, the free edge 222 of the valve leaflets 216 can be positioned at a predetermined location 238 along the middle region 208 of the frame 202. For example, as discussed herein, the predetermined location 238 can be positioned approximately at the maximum dimension of the middle cross-sectional area 210. In an additional embodiment, the predetermined location 238 can be positioned at a distance of at least twenty-five (25) percent from the inlet region 204 along the longitudinal center axis 242. For example, the predetermined location 238 can be positioned at a distance ranging from fifty (50) percent from the inlet region 204 to eighty (80) percent from the inlet region 204 along the longitudinal center axis 242. In addition, the predetermined location 238 can be positioned at a distance approximately eighty-five (85) percent from the inlet region 204 along the longitudinal center axis 242. The predetermined location 238 can also be positioned at a distance of greater than one hundred (100) percent from the inlet region 204 along the longitudinal center axis 242. In this embodiment, however, the valve leaflet 216 material must be chosen to resist thrombosis if it comes into contact with the frame 202 or the native vessel wall, as discussed more fully herein. Further, as the predetermined location 238 moves farther from the inlet region 204, the volume 232 of the sinus region 230 decreases, which may affect the backwash, as discussed herein.

The valve leaflet 216 of the present disclosure can be formed of various fluid impermeable, biocompatible materials including synthetic materials or biologic materials. Examples of synthetic materials include, but are not limited to: polyisobutylene-polystyrene (SIBS), polyurethane, poly(dimethylsiloxane) (PDMS), flouropolymer, proteins, polyethylene terephthalate (PET), protein analogs, copolymers of at least one of these materials, and other biologically stable and tissue-compatible materials as are known in the art. The materials may be formed by spinning, weaving, winding, solvent-forming, thermal forming, chemical forming, deposition, and combinations, include porous coatings, castings, moldings, felts, melds, foams, fibers, microparticles, agglomerations, and combinations thereof.

Possible biologic materials include, but are not limited to, autologous, allogeneic, or xenographt material. These include explanted veins and decellularized basement membrane materials (such as non-crosslinked bladder membrane or amnionic membrane), such as small intestine submucosa (SIS) or umbilical vein. As will be appreciated, blends or mixtures of two or more of the materials provided herein are possible. For example, SIBS could be blended with one or more basement membrane materials.

A material for the valve leaflets 216 can also include a fluid permeable open woven, or knit, physical configuration to allow for tissue in-growth and stabilization, and can have a fluid impermeable physical configuration.

The valve leaflets 216 may also be reinforced with high-strength materials. Examples of high-strength materials are nitinol, stainless steel, titanium, algiloy, elgiloy, carbon, cobalt chromium, other metals or alloys, PET, expanded polytetrafluoroethylene (ePTFE), polyimide, surlyn, and other materials known in the art. The high-strength materials may be in the form of wires, meshes, screens, weaves, braids, windings, coatings, or a combination. The high strength materials may be fabricated by methods such as drawing, winding, braiding, weaving, mechanical cutting, electrical discharge machining (EDM), thermal forming, chemical vapor deposition (CVD), laser cutting, e-beam cutting, chemical forming, and other processes known in the art. One embodiment includes CVD nitinol and wound or braided nitinol.

Suitable bioactive agents which may be incorporated with or utilized together with the valve leaflets 216 may be selected from silver antimicrobial agents, metallic antimicrobial materials, growth factors, cellular migration agents, cellular proliferation agents, anti-coagulant substances, stenosis inhibitors, thrombo-resistant agents, growth hormones, antiviral agents, anti-angiogenic agents, agents, growth hormones, antiviral agents, anti-tumor agents, angiogenic agents, anti-mitotic agents, anti-inflammatory agents, cell cycle regulating agents, genetic agents, cholesterol lowering agents, vasodilating agents, agents that interfere with endogenous vasoactive mechanisms, and hormones, their homologs, derivatives, fragments, pharmaceutical salts thereof, and combinations thereof. Specific examples are discussed herein.

Suitable bioactive agents which may be incorporated with or utilized together with the valve leaflets 216 can also include diagnostic agents or media such as radiologic contrast materials, MRI contrast agents, ultrasound contrast agents, or other imaging aids such as iodinated or non-iodinated contrast media, metallic materials such as gold, iridium, platinum, palladium, barium compounds, gadolinium, encapsulated gas, or silica.

Suitable biologically active materials are those than reduce tissue migration, proliferation, and hyperplacia, and include, but are not limited to, the following: paclitaxel, taxotere, rapamycin, sirolimus, and everolimus. Examples of resorbable materials include gelatin, alginate, PGA, PLLA, collagen, fibrin and other proteins. Examples of leakage-reducing materials include ePTFE, hydrophobic coatings, and bioresorbable layers. Materials such as elastin, acellular matrix proteins, decellularized small intestinal submucosa (SIS), and protein analogs, and certain polymers such as PTFE can perform multiple functions such as providing microporous material, leakage-reducing function, bioresorption, and/or facilitation of elution of biologically active material.

To decrease the risk of thrombosis, thrombo-resistant agents associated with the valve leaflets 216 may be selected from the following agents: heparin, heparin sulfate, hirudin, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, PPack (dextrophenylalanine proline arginine chloromethylketone), lytic agents, including urokinase and streptokinase, including their homologs, analogs, fragments, derivatives and pharmaceutical salts thereof.

Also, anti-coagulants may be selected from the following: D-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound, heparin, antithrombin compounds, platelet receptor antagonists, anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin, prostaglandin inhibitors, platelet inhibitors, tick antiplatelet peptides and combinations thereof.

In addition, suitable antibiotic agents include, but are not limited to, the following agents: penicillins, cephalosporins, vancomycins,aminoglycosides, quinolones, polymyxins, erythromycins, tetracyclines, chloramphenicols, clindamycins, lincomycins, sulfonamides, their homologs, analogs, derivatives, pharmaceutical salts and combinations thereof.

Anti-proliferative agents include, but are not limited to, the following: enoxaprin, angiopeptin, or monoclonal antibodies capable of blocking smooth muscle cell proliferation, hirudin, acetylsalicylic acid, and combinations thereof.

Useful vascular cell growth inhibitors include, but are not limited to, the following: growth factor inhibitors, growth factor receptor antagonists, transcriptional repressors, translational repressors, replication inhibitors, inhibitory antibodies, antibodies directed against growth factors, bifunctional molecules consisting of a growth factor and a cytotoxin, bifunctional molecules consisting of an antibody and a cytotoxin.

Suitable vascular cell growth promoters include, but are not limited to, transcriptional activators and transcriptional promoters.

Useful anti-tumor agents include, but are not limited to, the following: paclitaxel, docetaxel, taxotere, alkylating agents including mechlorethamine, chlorambucil, cyclophosphamide, melphalan and ifosfamide, antimetabolites including methotrexate, 6-mercaptopurine, 5-fluorouracil and cytarabine, plant alkaloids. including vinblastine, vincristine and etoposide, antibiotics including doxorubicin, daunomycin, bleomycin, and mitomycin, nitrosureas including carmustine and lomustine, inorganic ions including cisplatin, biological response modifiers including interferon, angiostatin agents and endostatin agents, enzymes including asparaginase, and hormones including tamoxifen and flutamide, their homologs, analogs, fragments, derivatives, pharmaceutical salts and combinations thereof.

Furthermore, anti-viral agents include, but are not limited to, amantadines, rimantadines, ribavirins, idoxuridines, vidarabines, trifluridines, acyclovirs, ganciclovirs, zidovudines, foscarnets, interferons, their homologs, analogs, fragments, derivatives, pharmaceutical salts and mixtures thereof.

Useful anti-inflammatory agents include agents such as: dexametbasone, prednisolone, corticosterone, budesonide, estrogen, sulfasalazine, mesalamine, and combinations thereof.

In one embodiment, an anti-mitotic agent may be radioactive material coupled to a biologically compatible carrier. In particular, the radioactive material may be selected from alpha-particle emitting isotopes and beta-particle emitting isotopes. Useful beta-particle emitting isotopes for treatment are generally selected from ³²P, ¹³¹I, ⁹⁰Y and mixtures thereof.

In other embodiments, the bioactive agent(s) associated with the valve leaflet 216 of the present disclosure may be a genetic agent. Examples of genetic agents include DNA, anti-sense DNA, and anti-sense RNA. DNA encoding one of the following may be particularly useful in association with an implantable device according to the present invention: (a) tRNA or rRNA to replace defective or deficient endogenous molecules; (b) angiogenic factors including growth factors such as acidic and basic fibroblast growth factors, vascular endothelial growth factor, epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, platelet-derived endothelial growth factor, platelet-derived growth factor, tumor necrosis factor alpha, hepatocyte growth factor and insulin-like growth factor; (c) cell cycle inhibitors; (d) thymidine kinase and other agents useful for interfering with cell proliferation; and (e) the family of bone morphogenic proteins. Moreover DNA encoding for molecules capable of inducing an upstream or downstream effect of a bone morphogenic protein may be useful.

The valve leaflets 216 may also be treated and/or coated with any number of surface or material treatments. For example, the valve leaflets 216 can be treated with one or more biologically active compounds and/or materials that may promote and/or inhibit endothelization and/or smooth muscle cell growth of the valve leaflets 216. Examples of such coatings include, but are not limited to, polyglactic acid, poly-L-lactic acid, glycol-compounds, and lipid compounds. Additionally, coatings can include medications, genetic agents, chemical agents, and/or other materials and additives. In addition, agents that limit or decrease cellular proliferation can be useful. Similarly, the valve leaflets 216 may be seeded and covered with cultured tissue cells (e.g., endothelial cells) derived from a either a donor or the host patient which are attached to the valve leaflets 216. The cultured tissue cells may be initially positioned to extend either partially or fully over the valve leaflets 216.

Valve leaflets 216 can also be capable of inhibiting thrombus formation. Additionally, valve leaflets 216 may either prevent or facilitate tissue in growth there through, as the particular application for the valve 200 may dictate. For example, valve leaflets 216 on the first outflow surface 220 may be formed from a porous material to facilitate tissue in growth there through, while valve leaflets 216 on the first inflow surface 218 may be formed from a material or a treated material which inhibits tissue ingrowth.

In one embodiment, the valve leaflet 216 material chosen can have some dependency on the configuration of the frame 202. As discussed herein, the frame 202 can be designed to resist collapsing under contraction of the calf muscle. In this embodiment, the material of the valve leaflet 216 can be non-elastic since the frame 202 in the middle region 208 remains approximately the same shape. However, in embodiments where the frame 202 is designed to collapse in a predetermined way under contraction of the muscle, the valve leaflet 216 can be an elastic material so that the valve leaflet 216 attachment locations 238 remain intact while the valve leaflet 216 maintains the ability to shift from the open position to the closed position, as discussed herein. In other embodiments, the elasticity of the valve leaflet 216 material can be dependent on the flexibility of the frame 202.

In an additional embodiment, the material of the valve leaflets 216 can be sufficiently thin and pliable so as to permit radially-collapsing of the valve leaflets 216 for delivery by catheter to a location within a body lumen, as discussed herein.

FIG. 2 also illustrates the venous valve 200 of the present disclosure where the valve leaflet 216 has a valve leaflet length 244 and a valve leaflet width 246. The valve leaflet width 246 can be measured between two predetermined locations 238 of the free edge 222 on a plane 248 extending perpendicularly from the longitudinal center axis 242 where the distance is greatest. The valve leaflet length 244 can be measured along the inflow surface 218 where the distance between the free edge 222 and an attachment location 234 of the valve leaflet 216 is greatest. The valve leaflet length 244 will be discussed more fully herein. In one embodiment, the valve leaflets 216 can have a ratio of valve leaflet length 244 to valve leaflet width 246. For example, the ratio of valve leaflet length 244 to valve leaflet width 246 can range from 0.75:1 to 1.5:1. In another embodiment, the ratio of valve leaflet length 244 to valve leaflet width 246 can be greater than 1.5:1. In an additional embodiment, the ratio of valve leaflet length 244 to valve leaflet width 246 can be less than 0.75:1.

FIG. 3 is an illustration of a portion of the venous valve 300 cut along the longitudinal center axis 3-3 in FIG. 1 to show the valve leaflets 316 connected to the frame 302 in the open position, as discussed herein. As discussed herein, specific dimensional relationships for the valve leaflets 316 and the middle region 308 of the frame 302 exist. For example, as illustrated, the valve leaflets 316 in their open configuration define a gap 350 between the free edge 322 of the valve leaflets 316 and the middle region 308 of the frame 302. The gap 350 is measured perpendicular to the longitudinal center axis 342, and in one embodiment, can have a maximum distance from the free edge 322 of the valve leaflets 316 to the middle region 308 of the frame 302 ranging from 0.5 millimeters (mm) to four (4) mm. In an additional embodiment, the gap 350 can have a maximum distance ranging from one (1) to three (3) mm. In yet another embodiment, the gap can have a maximum distance ranging from 1.5 to 2.5 mm. In addition, the distance of the gap 350 between each valve leaflet 316 and the frame 302 can be, but is not necessarily, equal.

In addition to the described maximum distance range of the gap 350, the gap 350 can also be dependent on the inlet diameter 352 of the inlet cross-sectional area 306. In one embodiment, the inlet cross-sectional area 306 can range from six (6) to eighteen (18) millimeters (mm). In an additional embodiment, the inlet cross-sectional area 306 can range from eight (8) to fifteen (15) mm. In yet another embodiment, the inlet cross-sectional area 306 can range from eight (8) to twelve (12) mm.

As discussed herein, the valve leaflets have a first inflow surface 318 and a first outflow surface 320 opposite the inflow surface 318. In addition, as discussed herein, the valve leaflets 316 have a valve leaflet length 344. The valve leaflet length 344 is measured along the inflow surface 318 of the valve leaflet 316 where the distance between the free edge 322 and an attachment location 134 to the frame 302 perpendicular to the free edge 322 in the middle region 308 is greatest. In one embodiment, the valve leaflet length 344 can be configured so that, in the closed position, approximately twenty (20) percent of the inflow surface 318 of the valve leaflets 316 overlap to form a fluid tight commissure.

In one embodiment, the valve leaflet length 344 (L) is be a function of the inlet radius 354 (r_(i)) of the inlet cross-sectional area 306, and can be at least equal to the inlet radius 354 (r_(i)). In another embodiment, the valve leaflet length 344 (L) is a function of the inlet radius 354 (r_(i)), where the function can range from L=1.2r_(i) to L=8r_(i). In an additional embodiment, the valve leaflet length 375 (L) is a function of the inlet radius 354 (ri), where the function can range from L=1.5r_(i) to L=5r_(i).

As will be understood by those skilled in the art, the valve 300 can be placed within a body lumen of the venous system by introducing a catheter into the venous system of the patient using a minimally invasive percutaneous, transluminal catheter based delivery system, as is known in the art. For example, a guidewire can be positioned within a body lumen of a patient that includes the predetermined location. The catheter, including valve 300, as described herein, can be positioned over the guidewire and the catheter advanced so as to position the valve 300 at or adjacent a predetermined location.

Although specific details regarding embodiments of the venous valve 300 have been discussed in relation to the venous valve 300 itself, embodiments of the present disclosure can also vary in relation to the size of the body lumen in which the valve 300 is to be placed. For example, in one embodiment, the middle cross-sectional area 310 can be larger than the body lumen cross sectional area and the inlet and outlet cross sectional-areas 306, 314 are approximately equal to the body lumen cross-sectional area. In this embodiment, the middle region 308 will expand the body lumen. In an additional embodiment, the inlet, middle, and outlet cross-sectional areas 306, 310, 314 can be smaller than the body lumen cross-sectional area. Different combinations of cross-sectional area sizes (e.g., inlet cross-sectional area 306, etc.) with respect to the body lumen are also possible.

The venous valve 300 of the present disclosure has been shown and described in detail including three regions, the inlet region 304, the middle region 308, and the outlet region 312. Additional embodiments of the present disclosure also include a venous valve 300 with less than three regions. For example, in one embodiment, the frame 302 can be designed to include an inlet region 304 and a middle region 308 such that the middle cross-sectional area 310 is larger than the inlet cross-sectional area 306. In this embodiment, the middle cross-sectional area 310 may be larger than the body lumen cross-sectional area and the inlet cross-sectional area 306 can be approximately equal to the body lumen cross-sectional area, and the valve leaflets 316 extend effectively from the middle region 308 into the body lumen. Other embodiments with more than three regions are also possible.

In addition, different combinations of cross-sectional area sizes (e.g., inlet cross-sectional area 306) with respect to the body lumen are also possible. Further, different combinations of cross-sectional area sizes (e.g., inlet cross-sectional area 306, etc.) with respect to other regions in the venous valve 300 are also possible.

While the present disclosure has been shown and described in detail above, it will be clear to the person skilled in the art that changes and modifications may be made without departing from the scope of the disclosure. As such, that which is set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the disclosure is intended to be defined by the following claims, along with the full range of equivalents to which such claims are entitled.

In addition, one of ordinary skill in the art will appreciate upon reading and understanding this disclosure that other variations for the disclosure described herein can be included within the scope of the present disclosure. For example, the frame 302 and/or the valve leaflets 316 can be coated with a non-thrombogenic biocompatible material, as are known or will be known.

In the foregoing Detailed Description, various features are grouped together in several embodiments for the purpose of streamlining the disclosure. This method of disclosure is not to be interpreted as reflecting an intention that the embodiments of the disclosure require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separate embodiment. 

1. A venous valve, comprising: a structural member having an inlet region that defines an inlet cross sectional area, a middle region that defines a middle cross sectional area, and an outlet region that defines an outlet cross sectional area, the inlet cross sectional area being different than the middle cross sectional area, and the inlet cross sectional area being at least approximately equal to the outlet cross sectional area; a first valve leaflet connected to the structural member, the first valve leaflet including a first inflow surface and a first outflow surface opposite the first inflow surface, and being configured to shift between an open position and a closed position; and a sinus defined by a volume between the structural member at the middle cross sectional area and the first outflow surface of the first valve leaflet in the open position.
 2. The venous valve of claim 1, including a second valve leaflet connected to the structural member opposite the first valve leaflet, where the first valve leaflet and the second valve leaflet have free edges in the sinus that in the open position form a free edge cross sectional area.
 3. The venous valve of claim 2, where the inlet cross sectional area is approximately equal to the outlet cross sectional area, is greater than the free edge cross sectional area, and is less than the middle cross sectional area.
 4. The venous valve of claim 2, where the middle cross sectional area is greater than the inlet cross sectional area and is approximately equal to the outlet cross sectional area and the inlet cross sectional area is greater than the free edge cross sectional area.
 5. The venous valve of claim 2, where the inlet cross sectional area is approximately equal to both the free edge cross sectional area and the outlet cross sectional area, and the inlet cross sectional area is less than the middle cross sectional area.
 6. The venous valve of claim 2, where the inlet cross sectional area is approximately equal to the outlet cross sectional area, the inlet cross sectional area is greater than the middle cross sectional area, and the middle cross sectional area is greater than the free edge cross sectional area.
 7. The venous valve of claim 2, where the structural member provides for a longitudinal center axis extending from the inlet region to the outlet region, the free edge of the first and second valve leaflet extending from an attachment location on the structural member at a distance at least twenty-five (25) percent from the inlet region along the longitudinal center axis.
 8. The venous valve of claim 7, where the attachment location on the structural member ranges from a distance fifty (50) percent from the inlet region to eighty (80) percent from the inlet region along the longitudinal center axis.
 9. The venous valve of claim 2, where the structural member provides for a longitudinal center axis, where the free edge of the first or second valve leaflet in the open position and the middle region of the structural member define a gap having a maximum distance ranging from 0.5 to four (4) millimeters (mm) measured perpendicular to the longitudinal center axis.
 10. The venous valve of claim 9, where the gap has a maximum distance ranging from one (1) to three (3) mm.
 11. The venous valve of claim 10, where the maximum distance ranges from 1.5 to 2.5 mm.
 12. The venous valve of claim 2, where the first and second valve leaflets have a valve leaflet length (L) along the inflow surface measured at a greatest length distance between the free edge and an attachment location to the structural member perpendicular to the free edge, where the inlet cross sectional area has an inlet radius (r_(i)), and where the valve leaflet length (L) is a function of the inlet radius (r_(i)) and is at least approximately equal to the inlet radius (r_(i)).
 13. The venous valve of claim 12, where the valve leaflet length (L) is a function of the inlet radius (r_(i)) that ranges from L=1.2r_(i) to L=8r_(i).
 14. The venous valve of claim 13, where the function ranges from L=1.5r_(i) to L=5r_(i).
 15. The venous valve of claim 2, where the structural member provides for a longitudinal center axis, where the first and second valve leaflets have a valve leaflet width (W) measured at a greatest width distance between attachment locations to the structural member existing on a plane extending perpendicularly from the longitudinal center axis, and where the first and second valve leaflets have a valve leaflet length (L) along the inflow surface measured at a greatest length distance between the free edge and an attachment location to the structural member perpendicular to the free edge, and the ratio of valve leaflet length (L) to the valve leaflet width (W) ranges from 0.75:1 to 1.5:1.
 16. The venous valve of claim 15, where the ratio of valve leaflet length (L) to valve leaflet width (W) is between 0.75:1 and 1.5:1.
 17. The venous valve of claim 1, where the first valve leaflet is formed of a material selected from the group comprising urinary bladder matrix (UBM), expanded polytetrafluoroethylene (ePTFE), polyurethane, silicone, polystyrene, and a cellurized tissue from a human, an animal, or a plant source.
 18. The venous valve of claim 16, where the material is reinforced with a metal mesh.
 19. A method, comprising: forming a middle region in a venous valve frame with an inlet region and a outlet region, the middle region being substantially different than the inlet region, and the inlet region being at least approximately equal to the outlet region; and coupling valve leaflets to the venous valve frame, where a free edge of the valve leaflets are located adjacent the middle region to form a sinus between the middle region in the venous valve frame and the valve leaflets.
 20. The method of claim 19, including configuring an opening defined by the valve leaflet to create a Bernoulli effect across the valve leaflet.
 21. The method of claim 19, where coupling the valve leaflet to the venous valve frame includes providing a gap of at least a predetermined distance between the free edge of the valve leaflet and the middle region in the venous valve frame.
 22. The method of claim 21, where coupling the valve leaflet to the venous valve frame includes maintaining at least the gap between the free edge of the valve leaflet and the middle region in the venous valve frame as the valve leaflet cycles between an open position and a closed position.
 23. The method of claim 19, where the venous valve frame resists flexing and can withstand a high expansion force on the middle region and a low expansion force on the inlet region and outlet region.
 24. The method of claim 19, where the venous valve frame is flexible and the valve leaflet is made of an elastomeric material.
 25. The method of claim 19, where the venous valve frame is flexible and the valve leaflet is large enough to maintain the closed position when the venous valve frame is compressed. 